The aim of the proposed research is the elucidation of the mechanism of adenosylcobalamin-dependent enzymatic reactions. We propose to characterize the substrate, allosteric and coenzyme binding sites of ribonucleotide reductase. We have developed analogs of the nucleotide substrates and the coenzyme which may modify the enzyme covalently. We are also characterizing thioredoxin and thioredoxin-reductase which with NADPH provide the reducing system for ribonucleotide reductase. In collaboration with Dr. Matwiyoff's group in Los Alamos we are studying the mechanism of epimerization of the corrins.